Residency · Residency · Medicine Pediatrics

Thyroid Disorders Across the Lifespan

Overview

Thyroid disorders span from congenital hypothyroidism detected by newborn screening to Graves disease in young adults to thyroid nodule management in older adults. The Med-Peds physician must understand age-specific presentations, the critical importance of neonatal thyroid screening, and the evolving approach to thyroid nodule evaluation that differs between pediatric and adult practice.

Thyroid Physiology

Hypothalamic-pituitary-thyroid (HPT) axis: TRH --> TSH --> T4/T3. T4 is the predominant secreted thyroid hormone (90%); converted to active T3 peripherally by deiodinases. Free T4 is the biologically active fraction (unbound to thyroxine-binding globulin) TSH is the most sensitive marker of thyroid function; inverse log-linear relationship with free T4. Thyroid hormones are critical for brain development (especially in the first 2-3 years of life), growth, metabolism, and cardiovascular function.

Congenital Hypothyroidism

Epidemiology and Etiology

Incidence: 1:2000-1:4000 newborns; most common preventable cause of intellectual disability. Thyroid dysgenesis (75-80%): ectopic thyroid, thyroid aplasia/hypoplasia; most cases are sporadic. Thyroid dyshormonogenesis (15-20%): autosomal recessive defects in thyroid hormone synthesis (most commonly thyroid peroxidase mutations) Central hypothyroidism (<5%): pituitary or hypothalamic deficiency; NOT detected by TSH-based screening alone. Transient hypothyroidism: maternal antibodies, iodine deficiency/excess, medications.

Newborn Screening

Universal newborn screening: one of the most successful public health interventions. Methods: primary TSH (most common worldwide), primary T4, or combined T4 + TSH. Timing: heel-stick blood spot at 24-48 hours of life; too early may detect physiologic TSH surge. Abnormal screen: elevated TSH (>20-40 mU/L depending on assay) and/or low T4. Confirmatory testing: serum TSH and free T4 within 24 hours if screen abnormal; thyroid ultrasound and/or nuclear scan to determine anatomy.

Management

Levothyroxine (L-T4): start immediately upon confirmation; do NOT delay treatment while awaiting imaging. Starting dose: 10-15 mcg/kg/day in neonates (higher per kg than older children or adults) Crush tablet in breast milk or water; do NOT mix with soy formula (impairs absorption) Goal: normalize TSH and maintain free T4 in upper half of normal range within 2-4 weeks. Follow-up: TSH and free T4 at 2-4 weeks, then every 1-2 months in first year, every 3-4 months in years 1-3, then every 6-12 months. Re-evaluation at age 3: trial off levothyroxine for 30 days with repeat TSH/free T4 to determine if hypothyroidism is permanent (in cases without clear permanent etiology) Outcomes: if treated within first 2 weeks of life, normal intellectual development expected; delayed treatment leads to irreversible neurodevelopmental impairment.

Acquired Hypothyroidism

Hashimoto Thyroiditis (Autoimmune Thyroiditis)

Most common cause of acquired hypothyroidism in both children and adults in iodine-sufficient areas. Pathology: lymphocytic infiltration, follicular destruction, fibrosis. Autoantibodies: anti-TPO (thyroid peroxidase, most common), anti-thyroglobulin. Pediatric presentation: goiter (often the presenting sign), growth deceleration, weight gain, fatigue, cold intolerance, constipation, delayed puberty, poor school performance; precocious puberty (rare, Van Wyk-Grumbach syndrome) Adult presentation: fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss, menstrual irregularities, depression, cognitive slowing, myxedema. Associated conditions: other autoimmune diseases (T1DM, celiac, vitiligo, Addison disease), Turner syndrome, Down syndrome.

Subclinical Hypothyroidism

Elevated TSH with normal free T4. Pediatric: TSH 5-10 mU/L may be monitored without treatment if asymptomatic; treat if TSH >10, symptoms present, goiter, growth deceleration, or dyslipidemia. Adult: treat if TSH >10; consider treatment if TSH 5-10 with symptoms, positive anti-TPO, pregnancy planning, or cardiovascular risk; controversial for mild elevation in elderly (TRUST trial showed no benefit of treatment in elderly with mild subclinical hypothyroidism)

Treatment

Levothyroxine: mainstay across all ages. Take on empty stomach, 30-60 minutes before food; separate from calcium, iron, PPIs by 4 hours. TSH target: 0.5-2.5 mU/L for most patients; upper normal range acceptable in elderly.

Hyperthyroidism

Graves Disease

Most common cause of hyperthyroidism in both children and adults. Pathology: TSH receptor-stimulating antibodies (TRAb/TSI) causing diffuse thyroid hyperfunction. Pediatric Graves: peak incidence in adolescence; female > male; presentation includes goiter, tachycardia, weight loss, heat intolerance, emotional lability, school performance decline, proptosis (less common than adults), accelerated growth and advanced bone age. Adult Graves: similar symptoms plus ophthalmopathy (30-50%), pretibial myxedema (rare), thyroid acropachy. Neonatal Graves: transient, caused by transplacental transfer of maternal TRAb; presents days to weeks after birth; tachycardia, irritability, poor weight gain, goiter; self-limited (resolves as maternal antibodies clear)

Diagnosis

TSH suppressed (<0.1 mU/L), elevated free T4 and/or free T3. TSH receptor antibodies (TRAb/TSI): confirm Graves disease; elevated in >95%. Radioactive iodine uptake (RAIU): diffusely increased uptake in Graves (vs. decreased in thyroiditis, nodular in toxic adenoma) Thyroid ultrasound: diffusely enlarged, increased vascularity (thyroid inferno on Doppler)

Management of Graves Disease

Antithyroid Drugs (ATD)

Methimazole: preferred in both children and adults (once daily dosing, better side effect profile than PTU) Pediatric dose: 0.2-0.5 mg/kg/day (max 30 mg/day) Adult dose: 10-30 mg/day initially, then titrate to maintenance 5-10 mg. Propylthiouracil (PTU): AVOID as first-line (hepatotoxicity risk, FDA black box); ONLY use in first trimester of pregnancy (methimazole is teratogenic: aplasia cutis, choanal atresia) or thyroid storm. Side effects: agranulocytosis (0.3-0.5%, potentially fatal; check CBC if fever/sore throat), hepatotoxicity (PTU >> methimazole), rash, arthralgia. Duration: 1-2 years in adults; 1-2+ years in children (longer courses may increase remission rates; many pediatric endocrinologists treat for extended periods) Remission rate: 40-60% adults after 12-18 months; 20-30% children (lower remission rate, often need definitive therapy)

Radioactive Iodine (RAI)

Definitive therapy; results in permanent hypothyroidism (requiring lifelong levothyroxine) Adults: commonly used first-line or after ATD failure; safe and effective. Children: generally reserved for age >10 (some centers >5); contraindicated in pregnancy; radiation safety precautions; avoid if Graves ophthalmopathy (may worsen)

Thyroidectomy

Total or near-total thyroidectomy by experienced surgeon. Indications: large goiter, failed ATD, contraindication to RAI, thyroid nodule suspicion, patient preference. Complications: hypoparathyroidism (transient 10-20%, permanent 1-2%), recurrent laryngeal nerve injury (<1%), bleeding. Pediatric: increasingly considered earlier in disease course; performed by high-volume thyroid surgeons.

Adjunctive Therapy

Beta-blockers (propranolol, atenolol): symptomatic relief of tachycardia, tremor, anxiety; use until euthyroid on ATDs. Pediatric dosing: propranolol 1-2 mg/kg/day divided TID-QID; atenolol 1-2 mg/kg/day.

Thyroid Storm

Life-threatening thyrotoxicosis with end-organ dysfunction. Triggers: surgery, infection, DKA, iodine load, non-adherence to ATDs. Presentation: fever >104F, tachycardia/arrhythmia (AF), altered mental status, GI symptoms (nausea, vomiting, diarrhea), heart failure. Management (sequential): Beta-blockade: propranolol IV or esmolol IV. PTU (preferred over methimazole in storm -- blocks T4-to-T3 conversion): 200-250 mg q4h. Iodine solution (SSKI or Lugol): 1 hour AFTER PTU (blocks new hormone release); if given before ATD, provides substrate for new hormone synthesis. Glucocorticoids: hydrocortisone 100 mg IV q8h or dexamethasone 2 mg q6h (inhibit T4-to-T3 conversion, treat relative adrenal insufficiency) Supportive: cooling, fluids, ICU care.

Thyroid Nodules

Pediatric vs. Adult Approach

Thyroid nodules are LESS common in children (1-2% prevalence) but MORE likely to be malignant (20-25% vs. 5-10% in adults) Pediatric thyroid cancer: papillary thyroid carcinoma (PTC) most common; often presents with cervical lymphadenopathy and lung metastases at diagnosis but still has excellent prognosis (>95% long-term survival) Evaluation approach is similar but the threshold for biopsy and surgery is lower in children.

Evaluation (Both Ages)

TSH: if suppressed, consider functioning nodule (hot nodule on thyroid scan -- rarely malignant) Thyroid ultrasound: assess size, features (hypoechoic, microcalcifications, irregular margins, taller than wide, extrathyroidal extension, suspicious lymph nodes) FNA biopsy: indicated for nodules >=1 cm with suspicious US features (adults) or >=1 cm in children (some experts biopsy smaller pediatric nodules) Bethesda classification: I (nondiagnostic), II (benign), III (AUS/FLUS), IV (follicular neoplasm), V (suspicious for malignancy), VI (malignant) Molecular testing (adult): Afirma, ThyroSeq; used for indeterminate cytology (Bethesda III/IV) to avoid unnecessary surgery; less validated in children.

Management

Bethesda II (benign): surveillance with serial US. Bethesda III/IV: repeat FNA, molecular testing, or diagnostic lobectomy. Bethesda V/VI: surgical excision (lobectomy or total thyroidectomy depending on size and risk factors) Active surveillance of low-risk papillary microcarcinoma: increasingly accepted in adults but NOT recommended in children.

<image>A lifespan timeline of thyroid disorders from birth to old age. Neonatal period shows congenital hypothyroidism with newborn screening heel-stick illustration. Childhood shows Hashimoto thyroiditis with goiter and growth chart deceleration. Adolescence shows Graves disease with thyroid eye signs and tachycardia. Young adulthood shows thyroid nodule evaluation with FNA biopsy illustration. Middle to older adulthood shows subclinical hypothyroidism management decisions and thyroid cancer surveillance. Each life stage includes the most common disorder, key diagnostic test, and first-line treatment.</image>

<image>A thyroid nodule evaluation comparison between pediatric and adult patients. Both pathways start with thyroid ultrasound showing suspicious features (labeled with ACR TI-RADS categories for adults and ATA pediatric risk stratification). The pediatric panel emphasizes higher malignancy risk (20-25%), lower size threshold for FNA, and more aggressive surgical approach. The adult panel shows TI-RADS-based FNA criteria, molecular testing for indeterminate cytology, and the option of active surveillance for low-risk microcarcinoma. The Bethesda classification system is shown centrally with management recommendations for each category across ages.</image>

<image>A treatment algorithm for Graves disease management across ages. Starting with diagnosis (suppressed TSH, elevated T4/T3, positive TRAb), the flowchart branches to three definitive treatment options: antithyroid drugs (methimazole first-line, ATD duration and remission rates compared between children and adults), radioactive iodine (age and contraindication considerations), and thyroidectomy (indications and complications). Beta-blocker adjunctive therapy is shown as initial symptomatic management. A separate emergency pathway shows thyroid storm management with sequential steps (beta-blocker, PTU, iodine, glucocorticoids) in red highlighting.</image>

Clinical Pearls

Congenital hypothyroidism is the most common preventable cause of intellectual disability -- treatment with levothyroxine within the first 2 weeks of life results in normal neurodevelopment. Neonatal levothyroxine dose (10-15 mcg/kg/day) is much HIGHER per kg than adult doses (1.6 mcg/kg/day) -- do not underdose neonates. Methimazole is the preferred antithyroid drug across all ages; PTU should be AVOIDED except in first trimester of pregnancy and thyroid storm (hepatotoxicity risk) In thyroid storm, give PTU BEFORE iodine -- iodine given before ATD provides substrate for new hormone synthesis and worsens the storm. Thyroid nodules are less common in children but more likely to be malignant (20-25% vs. 5-10% in adults) -- maintain a lower threshold for biopsy and surgical referral. Active surveillance of low-risk papillary microcarcinoma is increasingly accepted in adults but is NOT recommended in children. Hashimoto thyroiditis can cause both hypothyroidism AND transient hashitoxicosis (as thyroid follicles release preformed hormone during destruction) -- check TSH before starting treatment. Always check for associated autoimmune conditions in patients with Hashimoto thyroiditis (T1DM, celiac disease, adrenal insufficiency, vitiligo) Subclinical hypothyroidism in elderly patients may NOT require treatment -- the TRUST trial showed no benefit of levothyroxine in elderly with TSH 4.6-19.9.

References

• Leger J, Olivieri A, Donaldson M, et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm Res Paediatr. 2014;81(2):80-103.
• Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism. Thyroid. 2016;26(10):1343-1421.
• Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1-133.
• Francis GL, Waguespack SG, Bauer AJ, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer (ATA). Thyroid. 2015;25(7):716-759.
• Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2011;21(10):1081-1125.

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